This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Brain stroke ranks the third leading cause of death and disability in most developed countries, and is the second most common cause of death worldwide. Despite tremendous effort in thrombolysis and neuroprotection, no effective treatment is available for cerebral stroke in clinical settings. This is largely due to the inability of current treatments to repopulate the stroke lesion cavity with functional neurons and glia cells as substrates for structural repair. In support of this notion, neural transplantation strategies have been attempted to reconstruct the stroke cavity. Despite its efficacy in providing sustained functional recovery in the injured CNS, neural transplantation for cerebral stroke repair has had limited success, due to poor donor cell survival and functionality at the infarct site. In addition, ongoing hypoxia that is undergone by the ischemic tissue at the stroke lesion elevates tissue injury and inflammation. Our long-term goal is to rebuild the complete blood vessel network, followed by repopulation of the focal cerebral stroke lesion cavity with functional neural cells derived from human induced pluripotent stem cells (h-iPS) for sustained structural repair and functional recovery after cerebral stroke. The overall hypothesis is that a combined strategy based upon 1) complete reconstruction of blood vessel network at the stroke lesion zone, 2) repopulation of stroke zone with functional neural cells derived from h-iPS, and 3) suppressing scar formation surrounding the stroke lesion zone, would promote neural repopulation and host-integration at the stroke lesion zone, leading to significant improvement in neurological outcome in the cerebral stroke patients